Molecular diversity of pacemaker ion channels

Annu Rev Physiol. 2001:63:235-57. doi: 10.1146/annurev.physiol.63.1.235.


Ionic currents activated by hyperpolarization and regulated by cyclic nucleotides were first discovered more than 20 years ago. Recently the molecular identity of the underlying channels has been unveiled. The structural features of the protein sequences are discussed and related to the mechanisms of activation, selectivity for cyclic nucleotides, and ion permeation. Coverage includes a comparison of the biophysical properties of recombinant and native channels and their significance for the physiological functions of these channels.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Biological Clocks / physiology*
  • Cyclic Nucleotide-Gated Cation Channels
  • Genetic Variation*
  • Humans
  • Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels
  • Ion Channels / genetics*
  • Ion Channels / metabolism*
  • Molecular Sequence Data
  • Muscle Proteins*
  • Nerve Tissue Proteins*
  • Potassium Channels
  • Sequence Homology, Amino Acid
  • Sinoatrial Node / physiology


  • Cyclic Nucleotide-Gated Cation Channels
  • HCN4 protein, human
  • Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels
  • Ion Channels
  • Muscle Proteins
  • Nerve Tissue Proteins
  • Potassium Channels